Evaluation of compounds with antimalarial potential and study of the signal transduction mechanism of GPCR (G-Protein Coupled Receptor) like PfSR25 in Plasmodium falciparum

• Grant number: 20/08988-9
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): September 01, 2020
• Effective date (End): January 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Benedito Matheus dos Santos
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/08684-7 - Decoding Plasmodium signaling at molecular level as a new tool to the development of new antimalarials, AP.TEM

Abstract

Present in more than 90 countries, malaria is considered the most lethal infectious disease in the world. Epidemiological data released by WHO registered more than 228 million cases in 2018, resulting in 405,000 deaths worldwide. The issue of parasites' resistance to antimalarials spurs worldwide efforts to discover new drugs with possible inhibitory action on the development of Plasmodium falciparum. Our project intends to continue the search for antimalarial drugs, revealing its mechanism of action based on the screening of the library of synthetic compounds derived from the regioisomers 1H and 2H-1,2,3-triazole, using the strains P. falciparum 3D7 and knockout for the GPCR-like PfSR25. For this, we will use the transgenic P. falciparum parasite GCaMP3 for quantification of cytosolic calcium, and evaluate the impact of triazole compounds in P. falciparum mitochondria using the Mitoemerald-GFP construct. We also intend to evaluate the potential of these compounds to inhibit the differentiation of parasites of the asexual phase into gametocytes, using the NF54 strain. Our studies also include the comparative screening of compounds between the strains of P. falciparum 3D7 and PfSR25 knockout using the MMV library (Medicine for Malaria Venture) available in our laboratory. We believe that our studies will contribute to the understanding of the function of the GPCR-like PfSR25 receptor and also to the possible discovery of new drugs with antimalarial activity. (AU)